Reconsidering Long-Term Apirin in the Elderly in Secondary Prevention of Coronary Artery Disease Norway

NCT07854795 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 2026-526941-91-00
• Study Type: interventional
• Target: 7,000
• Locations: 1 country
• Sites: 9

Brief Summary

Lifelong aspirin has been a cornerstone of secondary prevention after coronary artery disease (CAD), based on trials conducted 40-50 years ago. Since then, major advances in coronary reperfusion and risk factor management have significantly improved outcomes. At the same time, aspirin is clearly associated with an increased risk of major bleeding, including intracranial haemorrhage. This raises a critical, yet unanswered question: in patients more than 2 years after a CAD event, does the benefit of continued aspirin still outweigh its bleeding risk? RELEASE-Norway is an investigator-initiated, registry-based, randomised trial with blinded endpoint assessment (PROBE design) designed to determine whether patients with chronic CAD can safely stop aspirin without losing cardiovascular protection. The trial will randomise 7,000 patients from all major hospitals in Norway. Together with a similar trial (RELEASE-Denmark, n≈7,000) planned in Denmark, the study will provide definitive evidence on the long-term net clinical benefit versus harm of aspirin in stable CAD and most likely directly inform future guidelines and clinical practice worldwide. Imaging and PROMS sub-studies will explore clinical and psychosocial mechanisms, providing insight into treatment heterogeneity and enabling future personalised antiplatelet therapy. Additionally, a health-economic analysis will assess the cost-effectiveness of discontinuing aspirin for healthcare systems.

Conditions

Coronary Arterial Disease (CAD)

Keywords

RELEASE; Aspirin; PCI

Outcome Measures

Primary Outcomes (1)

• Hierarchical composite endpont

  The net clinical benefit of discontinuing versus continuing aspirin in patients randomized 2-8 years after an index ACS event, using a hierarchical composite endpoint with a win-ratio framework that includes: 1. Cardiovascular death, 2. Intracranial bleeding, 3. Myocardial infarctions including stent thrombosis, 4. Ischemic stroke, 5. Major bleeding (BARC 3 and 5) requiring hospitalization. The components of the endpoints will be identified in The Norwegian Patient Registry and Cause of Death Registry using procedure and diagnostic codes.

  From randomization to median 3.0 (minimum 1.0) years follow-up

Secondary Outcomes (2)

• Risk of ischaemic disease

  From randomization to median 3.0 (minimum 1.0) years follow-up

• Risk of major bleedings

  From randomization to median 3.0 (minimum 1.0) years follow-up

Other Outcomes (16)

• Subgroup analyses

  From randomization to median 3.0 (minimum 1.0) years follow-up

• Risk of individual components of the primary endpoint

  From randomization to median 3.0 (minimum 1.0) years follow-up

• Recurrent CVD hospitalisations

  From randomization to median 3.0 (minimum 1.0) years follow-up

Study Arms (2)

Aspirin discontinuation

EXPERIMENTAL

Patients in the intervention group will be randomized to discontinuing aspirin treatment. The drug will be discontinued from their medical list. All participants will receive lifestyle advice and appropriate follow-up, as recommended.

Drug: Discontinuation of aspirin (ATC-code B01AC06 and N02BA01)

Aspirin continuation (ATC-codes B01AC06 and N02BA01)

NO INTERVENTION

Patients will be randomized to continuation of of low-dose oral aspirin (Anatomical Therapeutic Chemical codes B01AC06 and N02BA01) at a daily dose of ≤150 mg (usual care, no intervention). All participants will receive lifestyle advice and appropriate follow-up, as recommended.

Interventions

Discontinuation of aspirin (ATC-code B01AC06 and N02BA01) DRUG

Patients will be randomized open-label 1:1 to either continuation of low-dose oral aspirin (Anatomical Therapeutic Chemical codes B01AC06 and N02BA01) at a daily dose of ≤150 mg (no intervention group) or discontinuation of aspirin therapy (intervention group). If the patient is randomized to discontinuing aspirin the treatment will be discontinued from their medical list. All participants will receive lifestyle advice and appropriate follow-up, as recommended.

Aspirin discontinuation

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Age ≥65 years at randomization treated with low-dose (≤150 mg/day) aspirin
• An ACS event treated with PCI 2-8 years prior to randomisation and no ischemic cardiovascular event (MI or stroke) or any coronary revascularization procedure (PCI/coronary artery bypass grafting) since index event
• Signed informed consent and expected cooperation according to ICH/GCP and national/local regulations

You may not qualify if:

• Indication for antiplatelet treatment other than secondary prevention of CAD (i.e. haematological diseases, stroke, PAD)
• Active treatment with or indication for anti-coagulant or P2Y12-inhibitor therapy
• Left main stenosis or any history of stent thrombosis, or other contraindications to discontinuation of aspirin according to treating physician
• Any condition (e.g. drug/alcohol abuse, dementia) or situation, that in the investigator's opinion could put the subject at signifi-cant risk directly related to the randomized aspirin strategy, confound the results, interfere significantly with participation, or render informed consent unfeasible. Investigators are explicitly encouraged not to exclude patients solely due to advanced age, frailty or polypharmacy if equipoise exists regarding aspirin continuation vs. discontinuation and informed consent is feasible.
• Life expectancy \<12 months due to non-cardiac reasons or not being able to understand Norwegian or English language

Sponsors & Collaborators

• Vestre Viken Hospital Trust: lead
• Oslo Universitetssykehus Hospital Trust: collaborator
• Akershus University Hospital Trust: collaborator
• Sorlandet Hospital HF: collaborator
• Helse Stavanger HF: collaborator
• Helse-Bergen HF: collaborator
• St. Olavs Hospital: collaborator
• Norwegian Health Association: collaborator
• Landsforeningen for hjerte og lungesyke (LHL): collaborator
• Bispebjerg Hospital: collaborator
• Odense University Hospital: collaborator
• University of Oslo: collaborator
• University Hospital of North Norway: collaborator

Study Sites (9)

Sørlandet Hospital Trust Arendal

Arendal, 4838, Norway

Location

Haukeland University Hospital

Bergen, 5009, Norway

Location

Drammen hospital

Drammen, 3004, Norway

Location

Akershus University Hospital

Lørenskog, 1478, Norway

Location

Oslo University Hospital Rikshospitalet

Oslo, 0372, Norway

Location

Oslo University Hospital Ullevaal

Oslo, 0450, Norway

Location

Stavanger Universty Hospital

Stavanger, 4068, Norway

Location

University Hospital of North Norway Tromsø

Tromsø, 9019, Norway

Location

St. Olavs Hospital

Trondheim, 7030, Norway

Location

Study Officials

• John Munkhaugen, MD, PhD

  Vestre Viken HF

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John Munkhaugen, MD, PhD

CONTACT

+47 97524194; johmun@vestreviken.no

Ingrid Engebretsen, PhD

CONTACT

+4794406413; engebi@vestreviken.no

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Blinded end-point commitee
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2026
• First Posted: October 2, 2026
• Study Start (Estimated): February 1, 2027
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2031
• Last Updated: October 2, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

NO (9)